This invention relates to a new and useful method of chlorination in the field of pyridine chemistry, leading to an intermediate of known value in the synthesis of various sulfonylurea hypoglycemic agents. More particularly, it is concerned with a novel process for preparing 5-chloro-2-methoxynicotinic acid by chlorinating 2-methoxynicotinic acid at the 5-position of the molecule, thereby obtaining an intermediate known to be of value in the production of certain benzenesulfonylurea oral hypoglycemic agents.
In the past, 5-chloro-2-methoxynicotinic acid has been obtained by chlorinating 2-methoxynicotinic acid with chlorine per se in accordance with the method described by D. E. Kuhla et al. in U.S. Pat. No. 3,879,403. However, this method involves the use of chlorine gas with its associated potential hazards and the use of an aqueous solvent system which leads to heterogeneous reaction conditions with its attendant disadvantages. In the search for newer and more improved methods of production in this particular area, little is known about the use of other chlorinating agents with the pyridine ring system, even though these agents have been employed with variable success in the field of non-heterocyclic chemistry. For instance, alkali metal hypochlorite solutions have been used in the past to chlorinate nitroparaffins within a certain restricted pH range (e.g., pH 10-14) according to the method described by J. B. Tindall in U.S. Pat. No. 2,365,981, while similar solutions have also been employed in the chlorination of p-hydroxybiphenyl to give 3-chloro-4-hydroxybiphenyl according to the method of described.by E. F. Grether in U.S. Pat. No. 1,832,484.